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Complementary Therapies in Medicine (2014) 22, 614—620

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Exercise training and music therapy in


elderly with depressive syndrome:
A pilot study
W. Verrusio a,∗, P. Andreozzi a, B. Marigliano b, A. Renzi c,
V. Gianturco a, M.T. Pecci d, E. Ettorre a, M. Cacciafesta a,
N. Gueli a

a
Department of Cardiovascular, Respiratory, Nephrological, and Geriatric Sciences, Sapienza University of
Rome, Rome, Italy
b
Internal Medicine, Campus Bio-medico of Rome, Rome, Italy
c
Department of Dynamic and Clinical Psychology, ‘‘Sapienza’’ — University of Rome, Italy
d
‘‘Science of Aging’’ Interdepartmental Research Center — Sapienza University of Rome, Italy
Available online 6 June 2014

KEYWORDS Summary
Objective: Recent studies have thrown doubt on the true effectiveness of anti-depressants in
Anxiety;
light and moderate depression. The aim of this study is to evaluate the impact of physical train-
Depression;
ing and music therapy on a sample group of subjects affected by light to moderate depression
Exercise;
versus subjects treated with pharmacological therapy only.
Music therapy;
Design and setting: Randomized controlled study. Patients were randomized into two groups.
Elderly;
Subjects in the pharmacotherapy group received a therapy with antidepressant drugs; the exer-
Rehabilitation
cise/music therapy group was assigned to receive physical exercise training combined with
listening to music. The effects of interventions were assessed by differences in changes in
mood state between the two groups.
Main outcome measures: Medically eligible patients were screened with the Hamilton Anxiety
Scale and with the Geriatric Depression Scale. We used plasmatic cytokine dosage as a stress
marker.
Results: We recruited 24 subjects (mean age: 75.5 ± 7.4, 11 M/13 F). In the pharmacotherapy
group there was a significant improvement in anxiety only (p < 0.05) at 6-months. In the exer-
cise/music therapy was a reduction in anxiety and in depression at 3-months and at 6-months
(p < 0.05). We noted an average reduction of the level of TNF-a from 57.67 (±39.37) pg/ml to
35.80 (±26.18) pg/ml.

∗ Corresponding author at: Department of Cardiovascular, Respiratory, Nephrological, and Geriatric Sciences, Sapienza University of Rome,

Viale del Policlinico 155, 00161 Roma, Italy. Tel.: +39 3490745274.
E-mail address: walter.verrusio@uniroma1.it (W. Verrusio).

http://dx.doi.org/10.1016/j.ctim.2014.05.012
0965-2299/© 2014 Elsevier Ltd. All rights reserved.

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Exercise training and music therapy with depressive syndrome 615

Conclusions: Our training may potentially play a role in the treatment of subjects with mild to
moderate depression. Further research should be carried out to obtain more evidence on effects
of physical training and music therapy in depressed subjects.
© 2014 Elsevier Ltd. All rights reserved.

Introduction of light to moderate intensity, with a level of effective-


ness comparable to that of psychological or pharmacological
therapies, especially over the long term.11
Depression and anxiety are frequent disorders in the elderly.
In the present study, we used plasmatic cytokine dosage
Beyond the age of 65, the risk of falling ill with depression
as a stress marker. Recent research has pointed to an
increases threefold compared to the general population.1
active role on the part of pro-inflammatory cytokines in the
The Food and Drug Administration (FDA) recently released
regulation of synaptic plasticity, demonstrating that hyper-
the data underlying the approval of six of the most widely
activation of the immune system can be identified as part
sold anti-depressants: in 47 controlled clinical studies, only
of the pathogenesis of depression.12 Patients suffering from
10—20% showed benefits effectively attributable to the
mood disturbances have been found to present increases in
pharmacological action of the molecule employed, while
Interleukin 1 (IL1), Interleukin 6 (IL6) and Tumor Necrosis
the placebo effect was responsible for the improved mood
Factor alpha (TNF␣), tied to a greater risk of cognitive dis-
of 80—90% of the subjects.2 In confirmation of this find-
turbances and mood depression, plus a reduced response to
ing, a recent study showed that drugs against depression
therapy.13 The cytokine dosage, therefore, can be used as
proved partially effective only in subjects suffering from
a parameter for evaluating the effectiveness of a proposed
severe depression.3 In recent years, therefore, extensive
therapy.
scientific evidence has thrown doubt on the true effective-
The primary aim of this study is to determine whether
ness of anti-depressants, especially for patients affected by
exposure to music and physical training can have a positive
light or moderate depression. And we need, especially in the
effect on the mood of elderly subjects suffering from light
field of geriatrics, to look for new tools for the treatment of
to moderate depression, and whether the improvement in
mood disturbances.
mood persists over time.
Experience has been gained, over the last few years,
A secondary aim of the study is to evaluate the effec-
with cognitive therapy (CT). A study carried out on 240
tive influence of aerobic physical training on the concurrent
patients suffering from moderate to severe depression
disturbances of the subjects examined.
showed that, although the percentage of response to
treatment with CT overlapped, to a certain extent, with
the response to pharmaceuticals, the long-term incidence Materials and methods
of new episodes of depression in the group treated with
Selective serotonin reuptake inhibitors (SSRIs) was 54%, This was a randomized controlled trial. This study included
compared to 17% among patients treated with CT.4 This a series of elderly subjects (n = 24; mean age: 75.5 ± 7.4;
suggests not only that the effect of CT lasts longer than that 13 females) diagnosed according to the DSM-IV criteria with
of pharmaceuticals, but that CT can produce changes which major depression with mild to moderate severity.14,15 Each
differ from those brought about by pharmaceutical therapy, participant received information about this study in writing
making it a valid alternative to the use of anti-depressants. and an individual verbal explanation of this study from the
In the field of geriatrics, other works have highlighted the researcher. Participation was entirely voluntary. Individual
positive effect of music on treating cognitive disturbances5 participants in this study gave written informed consent and
and behavioral and psychological symptoms of dementia a signed declaration of consent. This study was conducted
(BPSD)6 and on a whole series of unfavorable stress-induced according to the principles expressed in the Declaration
circumstances, including anxiety and depression.7 Recent of Helsinki and was approved by the ‘‘Science of Aging’’
research efforts examining the effects of listening to music Interdepartmental Research Center of Sapienza University
on the brain have discovered that music is able to increase of Rome. We evaluated the concurrent conditions through
cerebral synaptic plasticity.8 In other words, though they the Cumulative Illness Rating Score (CIRS) and its Comor-
act through different mechanisms and have different bidity Index (CInd).16 The main diseases found in the test
effects, both depression and music work in a shared sub- group were: hypertension, obesity, diabetes mellitus, car-
strate of certain areas of the brain, giving rise to a series bohydrate intolerance, dyslipidemia. Consistency with the
of changes.9 The fact is that exposure to sound leads to following criteria of inclusion was assessed for each patient:
increased neurogenesis at the hippocampus, where neuron diagnosis of light to moderate depression, with a Geriatric
impoverishment due to loss and/or scarce regeneration is Depression Scale (GDS) score between 5 and 12; absence of
thought to be an underlying cause of a variety of mood pharmacological treatment. Patients suffering from severe
disturbances, including depression.10 Therefore there is a depression, or for whom physical exercise was not rec-
very close link between depression and music. ommended (blood pressure — SBP — >200 mmHg and/or
Another therapeutic strategy recently proposed for the diastolic blood pressure — DBP — >110 mmHg; diabetic
treatment of depressed subjects is physical activity. Physical subjects with fasting blood glucose — FBG — >250 mg/dl;
training helps control mood disturbances, especially those unstable angina pectoris; arrhythmias; severe heart valves

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616 W. Verrusio et al.

diseases; aneurysms; any kind of severe systemic diseases), For the portion of the study involving depression, the
were excluded. variations in mood were measured with the GDS, a brief
Participants were randomly assigned to the pharma- depression screening inventory composed of 15 items that
cotherapy group or the exercise/music therapy group using require yes or no answers. A score of 5 or more indicates
computerized random numbers. Group allocation was not depressed individuals.18 The state of anxiety was evaluated
communicated to the patients until the first exercise/music with the HAS. It consists of 14 items, each defined by a series
session or the first prescription of the drug. of symptoms. Each item is rated on a 5-point scale, ranging
An electronic chart was filled out for each subject, from 0 (not present) to 5 (severe). A score of 18 or more
recording the following parameters at the start of the study indicates anxiety.19
(W0), at the three-month point (W12), after six months An overall description was performed for each of the con-
(W24) and, finally, in the exercise/music therapy group at sidered variables. For qualitative variables, the frequencies
one month after the end of the study (W28): of each modality were determined. For quantitative vari-
ables mean and standard deviation were calculated. Mean
values were compared using Student’s t-test. The change in
- pharmacotherapy group: GDS for assessing mood; Hamil- the parameters between groups was compared by one-way
ton Anxiety Scale (HAS) score for evaluating anxiety; analysis of variance and HAS score at baseline was used as
- exercise/music therapy group: GDS and HAS; standard covariate (ANCOVA), to control the effect of this variable on
laboratory techniques were used to determine, after an outcome at 12 and 24 months (since it appeared marginally
overnight fast, plasma total cholesterol (TC), high-density different in the two groups). A 95% confidence intervals (CI)
lipoprotein cholesterol (HDLc), triglycerides (TG), FBG was calculated. A p value below 0.05 was deemed signifi-
and plasmatic cytokine dosage (TNF␣, IL1, IL6). Waist cir- cant.
cumference (WC) was measured at the level of iliac crest
with the patients standing. The body mass index (BMI) was
determined by dividing the weight (kg) by the square of Results
height (m).
24 patients were randomized into two groups: 12 subjects
into the pharmacotherapy group (mean age: 76.1 ± 7.1;
The pharmacotherapy group subjects were assigned to CInd: 2.4 ± 2.3; males/females: 4/8) and 12 subjects into
receive a antidepressant medication involving an SSRI in the exercise/music therapy group (mean age: 74.8 ± 8; CInd:
9 patients (paroxetine 20 mg/die) and a specific seroto- 2.1 ± 0.7; males/females: 7/5) (Fig. 1).
nergic antidepressant (NaSSA) in 2 patients (mirtazapine All patients completed the study protocol.
30 mg/die), associated with benzodiazepine (Alprazolam) as The characteristics of the patients including age, Comor-
needed. bidity Index, GDS and HAS scores were not significantly
The exercise/music therapy group subjects were different between the two groups at baseline.
assigned to receive physical exercise training combined Table 1 shows test scores in the two groups.
with listening to music. Each patient engaged in two In the pharmacotherapy group there were minimal varia-
sessions of physical exercise a week, with each session tions in GDS and HAS scores, however there was a significant
lasting approximately an hour. The routine consisted in: within group change in anxiety observed after 24 weeks com-
warm-up of muscles, general gymnastics or postural gym- pared to baseline data (p < 0.05) (Fig. 2). At 3-months, we
nastics, aerobic training on stationary bicycles or treadmills, prescribed in association therapy benzodiazepine (Alprazo-
post-workout decompression. The physical activity was mod- lam) to 6 patients and we increased antidepressant dosage
erately intense so as not to exceed the target pulse rate, in 4 patients (paroxetine, from 20 mg/die to 40 mg/die).
meaning 75% of the maximum pulse rate for the patient We also changed antidepressant therapy of 9 patients at
being treated (based on the theoretical maximum pulse rate 6-months because of side effects.
by age, or on the Borg scale).17 Blood pressure, resting heart In the exercise/music group there were significant within
rate, pulse oximetry and FBG were assessed before and after group reductions both in anxiety and in depression observed
exercise. While the patients exercised, a collection of musi- after 12 and 24 weeks compared to baseline data (p < 0.05)
cal pieces was played. Three different play-lists were used (Fig. 2). In general, the physical training in our study was
for the study, with the style of music selected in accor- well tolerated and the exercise/music group did not take
dance with the tastes of the patients, who were interviewed any antidepressant medication during study period.
during the recruitment phase. Three different genres were There were significant differences between the phar-
identified: Jazz (Mt.1), Classical (Mt.2), Modern (Mt.3). The macotherapy group and exercise/music group for HAS
sample group being examined was divided into 3 subgroups measurements at week 12 and at week 24 and for GDS at
of four patients each, one for each play-list. The different week 24 (p < 0.05), although the covariate for HAS at base-
songs on the various play-lists each corresponded to a spe- line was included (Table 1).
cific phase of the physical training session; each session was The cytokine dosages in the serum of the exercise/music
divided as follows: therapy group subjects examined pointed to a linear cor-
relation between high levels of cytokine and a high GDS
score. In fact, of the 12 patients examined, 9 presented a
• warm up (light exertion, slow rhythm),
average GDS score of 7.44 (±1.23) and undetectable doses
• main part (moderate-intense exertion, fast rhythm), of cytokines in the blood plasma, while 3 subjects showed
• cool down (decompression phase, slow rhythm). a average GDS score of 11.66 (±0.57) combined with high

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Exercise training and music therapy with depressive syndrome 617

Assessed for eligibility (n=24)

Excluded (n=0)

Αll participants assessed for eligibility met the


inclusion criteria

Randomized (n=24)

Allocated to Pharmacotherapy group (n=12) Allocated to Exercise/music therapy group


Received allocated intervention (n=12) (n=12)
Received allocated intervention (n=12)

Lost to follow-up (n=0) Lost to follow-up (n=0)

Continued follow up (n=12) Continued follow up (n=12)

Analysed (n=12) Analysed (n=12)

Figure 1 The study flow chart.

levels of TNF-␣. The following dosage reading, taken at 24 pressure (p < 0.05) and 3 mmHg in the average diastolic blood
weeks, showed that the average level of TNF-␣ in the three pressure of the group examined; a variation in the lipid level,
most depressed subjects had fallen from 57.67 (±39.37) with average reductions of 27 mg/dl in TC (p < 0.05) and of
pg/ml to 35.80 (±26.18) pg/ml. 14.75 mg/dl in the TG; a reduction of 16.7 mg/dl in the levels
A new assessment of mood carried out 4 weeks (W28) of basic FBG (p < 0.05); an average reduction of 6.2 cm in the
after the suspension of the rehabilitation program resulted WC of the sample group examined (Table 2).
in only minimal differences in the GDS and HAS scores. For
these parameters, the difference between W24 and W28 was
minimal (GDS: −0.17 ± 0.58; HAS: 0.17 ± 1.03). Discussion
As for the secondary aim of the study, after 6 months
we observed the following in the exercise/music therapy The primary aim of this study is to determine whether expo-
group: a reduction of 7 mmHg in the average systolic blood sure to music and physical training can have a positive effect

Table 1 Anxiety (HAS) and depression (GDS) in the two groups. Values at baseline (W0), 12 weeks later (W12), 24 weeks later
(W24) and differences between groups not-adjusted and adjusted for HAS score at baseline.

Pharmacotherapy Exercise/music Differences F; p F; p


group therapy group between groups Not-adjusted Adjusted
Mean (SD) Mean (SD) [95% CI] F p F p
HAS
W0 24.2 (±5.3) 22.2 (±5.07) −2.08 [−6.51 to 2.34] 0.95 0.34 / /
W12 23.5 (±3.5) 19.6 (±4.8) −3.92 [−7.50 to −0.33] 5.14 0.03 4.55 0.04
W24 22 (±4.7) 16.5 (±2.7) −5.50 [−8.80 to −2.20] 11.92 0.00 13.33 0.00
GDS
W0 8.4 (±1.8) 8.5 (±2.2) 0.09 [−1.97 to 2.14] 0.01 0.92 / /
W12 8.6 (±2.9) 7.6 (±1.6) −1.2 [−2.84 to 0.84] 1.08 0.31 1.74.20
W24 8 (±2.5) 5.5 (±1) −2.92 [−4.39 to −0.61] 10.44 0.01 8.72 0.01
p < 0.05 = significant.

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618 W. Verrusio et al.

Figure 2 Change in depression and anxiety scores. Means and standard deviation (error bars). GDS = Geriatric Depression Scale;
HAS = Hamilton Anxiety Scale. *Significant difference between the two groups.

on the mood of elderly subjects suffering from light to mod- analyzed the effect of music exposure or exercise training
erate depression and whether the improvement in mood on depression,21—23 but our study provides preliminary evi-
persists over time. The results at the third and sixth month dence of the combined benefit of exercise and listening to
show a twofold positive effect in the exercise/music therapy music for mood disturbances in elderly patients. For this
group, reducing both depression and the symptoms of anxi- reason we have chosen to study two groups of patients, a
ety in the group. We also observed progressive improvement pharmacotherapy group versus an exercise/music therapy
linked to an increase in the number of sessions, point- group, exploring directly synergistic therapy. However, when
ing to the possibility of a dose-dependent effect. On the analysing our results it is not possible to disentangle the con-
contrary, in the pharmacotherapy group we observed only tribution of each component to the overall effect. Secondly,
minimal variations in GDS and HAS scores at the third month although the very small number of test subjects means that
and we observed a significant reduction in anxiety only at the result cannot be considered statistically significant, the
6-months. variations in cytokines levels of our study are similar to
We assessed whether the positive results of our training findings reported in other studies that have pointed to a cor-
lasted over time, subjecting the subjects of the exer- relation between high levels of cytokines and depression.24
cise/music therapy group to a new control 4 weeks after These preliminary results seem to confirm that the cytokine
suspension of the rehabilitation program. The results for dosages in the serum may potentially play a role as indi-
both depression and anxiety showed only minimal differ- cator of effectiveness for evaluating the effectiveness of
ences in the GDS and HAS scores. With regard to physical a antidepressive therapy but further studies are needed to
training, our study shows that it has both a beneficial effect better characterize these correlations. Thirdly, the results
on mood and a positive influence on an entire series of con- of our training in the exercise/music therapy group, espe-
ditions that present a high rate of morbidity in the geriatric cially over the short term, can be attributed in part to the
age bracket. placebo effect, which, nevertheless, can be used to good
In light of these results, we hold that physical training advantage when treating depressed subjects, especially in
associated with exposure to music is capable of setting off the early phases of a rehabilitation program. For the placebo
a series of positive effects leading to modifications in both effect can encourage the depressed subject to take a more
the depressive and anxious components of the mood.20 active role in the healing process while helping to create
Nevertheless the current study faces certain limitations. a good physician—patient relationship, in this way creating
Firstly, the small size of the sample. Other studies have ideal conditions for pursuing the therapeutic strategy over

Table 2 Side effects of antidepressant medications and secondary effects of our rehabilitation program.

Antidepressant drugs Training (value W24)

MAOIs Hypertensive crisis, flushing, nausea • Reduction of 7 mmHg in the average systolic pressure
TCAs Constipation, weight gain, sexual dysfunction, and 3.2 mmHg in the average diastolic pressure;
dizziness, memory disturbances, sedation • Average reductions of 15% in total cholesterol and of
SSRIs Dyspepsia, nausea, sexual dysfunction 10% in the triglycerides;
NASSAs Weight gain, drowsiness, dizziness, headache • Reduction of 15% in the levels of basic glycaemia;
NARI Hypotension and tachycardia, insomnia, • Average reduction of 6.2 cm in the waist
urinary retention measurements
NSRIs Dyspepsia, nausea, constipation
MAOI, monoamine oxidase inhibitors; TCA, tricyclic antidepressants; SSRIs, selective serotonin reuptake inhibitors; NASSAs, noradrenergic
and specific serotonergic antidepressants; NARI, selective noradrenaline reuptake inhibitor; NSRIs, norepinephrine serotonin reuptake
inhibitors.

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Exercise training and music therapy with depressive syndrome 619

the long term, at which point the results will be influenced Further research should be carried out using a larger
to a lesser extent by the placebo effect. group of patients to obtain more evidence on effects of phys-
We feel that, despite the limitations of this pilot study, ical training and music therapy in rehabilitation of subjects
the results can have interesting implications for clinicians affected by light to moderate depression.
in the management of light and moderate depression.
It is known that modifications in the neuro-transmission
of elderly subjects render them more vulnerable to Conflict of interest
the extra-pyramidal and anticholinergic effects of anti-
depressant pharmaceuticals, resulting in the frequent onset The authors declare that they have no competing financial
of side effects.1 This also delays the construction of a interests.
physician—patient relationship that is important for the
management of depressed patients and requires more time
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